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STUDY ON THE MOLECULAR MECHANISM OF GLUCOCORTICOID HORMONE ACTION

Research Project

Project/Area Number 07671099
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionASAHIKAWA MEDICAL COLLEGE

Principal Investigator

TANAKA Hirotoshi  ASAHIKAWA MEDICAL COLLEGE,SECOND DEPARTMENT OF INTERNAL MEDICINE,ASSISTANT PROFESSOR OF MEDICINE, 医学部, 講師 (00171794)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsglucocorticoids / transcription factors / DNA binding protein / molecular biology / endocrinology / redox / トランスフェクション / ホルモン受容体
Research Abstract

The molecular mechanisms of glucocorticoid hormone action were studied with special reference to
1) regulation of glucocorticoid receptor expression.
2) interplay between the glucocorticoid receptor and transcription factors,
3) functional significance of post-translational modification of the glucocorticoid receptor.
1) Expression of the glucocorticoid receptor was negatively modulated by agonistic ligands, and this down-regulation of the glucocorticoid receptor was correlated with down-modulation of hormone responsiveness.
2) Interaction between the glucocorticoid receptor and CREB and AP-1 was biochemically characterized. Moreover, clinical importance of such factor interaction was clearly demonstrated by using thyroid cells and fibroblasts as model systems.
3) Redox-regulation of the glucocorticoid receptor was investigated. The cysteine residues of the receptor was shown to susceptible to oxidative stress, and thioredoxin, as an electron donor, potentiated the receptor mediated gene expression.
Together, the molecular understanding of hormone action was extensively advanced.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Takako Tani‐Kawakami: "Effect of 1α‐hydroxy vitamin D_3 on serum levels of thyroid horuones in patients with untreafed Graves's disease" Metabolism. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuichi Makino: "Thioredoxin:a redox regulating cellular ω factor for glucocorticoid hormone action" J. Clin. Invest.98. 2469-2477 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuichi Makino: "Modulation of the glucocorticoid receptor function by metal ions" Mol. Pharmacol.49. 612-620 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hirotoshi Tanaka: "Ligand‐independent activation of the glucocorticoid receptor by cosodesxycholic acid" J. Immunol.156. 1601-1608 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hirotoshi Tanaka: "Zinc ions antagonize the inhibitory effect of aurothiomalate on glucoanttcoid receptor function at physiological concertrations" Mil. Pharmacol.48. 938-945 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hirotoshi Tanaka: "Polentiation of glucowhioid-mediated gene expression by the novel benzoguinone denibative E3330" Eur. J. Pharmacol.291. 121-127 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takako Tani-Kawakami: "Effect of 1alpha-hydroxy vitamin D3 on serum levels of thyroid hormones in patients with untreated Graves' disease." Metabolism. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuichi Makino: "Thioredoxin : a redox-regulating cellular cofactor for glucocorticoid hormone action." J.Clin.Invest.98. 2469-2477 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuichi Makino: "Modulation of the glucocorticoid receptor function by metal ions." Mol.Pharmacol.49. 612-620 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hirotoshi Tanaka: "Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid" J.Immunol.156. 1601-1608 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fuminori Hirano: "Effects of ursodeoxycholic acid and chenodeoxycholic acid on major histocompatibility complex class I gene expression." J.Gastroenterol.31. 55-60 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fuminori Hirano: "Induction of the transcription factor AP-1 in cultured colon adenocarcinoma cells following exposure to bile acids." Carcinogenesis. 17. 427-433 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hirotoshi Tanaka: "Zinc ions antagonize the inhibitory effect of aurothiomalate on glucocorticoid receptor function at physiological concentrations." Mol.Pharmacol.48. 938-945 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hirotoshi Tanaka: "Potentiation of glucocorticoid-mediated gene expression by the novel benzoquinone derivative (2E) -3- [5- (2,3-dimethoxy-O-methyl-1,4-benzoquinoyl)] -2-nonyl-2-propenoic acid (E3330)." Eur.J.Pharmacol. 291. 121-127 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fuminori Hirano: "Regulation of the major histocompatibility complex class I mRNA expression by bile acids in cultured human hepatoma cells." Biochem. Biophys.Res.Commun.208. 935-942 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takako Tani-Kawakami: "Effect of 1α-hydroxy vitamin D_3 on serum levels of thyroid hormons in patients with untreated Graves' disease" Metabolism. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yuichi Makino: "Thioredoxin : aredox-regulating cellular cofactor for glucacorticoid hormone ation" J.Clin.Invest.98. 2469-2477 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yuichi Makino: "Modulation of the glucocorticoid receptor function by metal ions" Mol.Pharmacol.49. 612-620 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirotoshi Tanaka: "Ligand-independent activation of the glucocorticoid receptor by ursodesxycholic acid" J.Immunol.156. 1601-1608 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirotoshi Tanaka: "Zinc ions antagonize the Thhibitory effect of Qurothionalate on alues coticoid receptor function at physiological concentrations" Mol.Pharmacol.48. 938-945 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirotoshi Tanaka: "Polentiatin of glunowticoid-mediated gene expression by the novel benzoguinone derivative E3330" Eur.J.Pharmacol.291. 121-127 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka H.et al: "Ligand-independent activation of the glucocorticoid receptor" J.Immunol.(印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tanaka H et al: "Zinc Tons antagoinze the inhibitony effect of aurothiomalateon glucocorticoid receptorfunction at physiological concentrations" Mol.Pharmacol.48. 938-945 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tanaka H et al: "Polentiation of glucocorticoid-mediated gene expression by the novel benzoquinone derivative E3330" Eun J.Pharmacol.291. 121-127 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirano F et al: "Indnction of the transaription factor AP-1 in cultured human colon adenocarcinoma cells following exposure to bile acids." Carcinogenesis. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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